Endothelin-1:
Endothelin is a long-acting, highly powerful vasoconstrictor found
throughout the brain. Endothelin helps to the maintenance of CBF by
working through its receptors, ETA and ETB, and is regarded as a major
auto regulating peptide (Graves & Kreipke, 2015). ET-1 is a peptide
that is generated and released by the vascular endothelium in response
to substances like reactive oxygen species (ROS), cytokines, and
thrombin. ET-1 is also known to be produced by leukocytes and
macrophages (Fassbender et al., 2000). Although endothelin-1 is widely
acknowledged as a strong vasoconstrictor, its precise role in
autoregulation appears to be more elusive. Adults with elevated ET-1
levels in the CSF after TBI had poor clinical outcomes, including death,
permanent vegetative state, or severe debility, according to data
acquired by (Maier, Lehnert, Laurer & Marzi, 2007) Endothelin-1 has
been associated to reduced CBF and poor prognosis post damage in several
animal models of TBI. According to the findings of the following studies
(Armstead & Kreipke, 2011; Beuth, Kasprzak, Kotschy, Woźniak, Kulwas &
Sniegocki, 2001; Kreipke, Morgan, Roberts, Bagchi & Rafols, 2007;
Lampl, Fleminger, Gilad, Galron, Sarova-Pinhas & Sokolovsky, 1997;
Salonia et al., 2010; Sato & Noble, 1998), TBI disrupts autoregulatory
systems by increasing endothelin-1-mediated vasoconstriction. Further
studies revealed that, while the drug significantly reduced vasospasm,
it did not result in significant improvements in the patient’s
condition, showing that vasospasm may not be the primary cause of poor
outcome after subarachnoid hemorrhage but early brain injury may also be
a factor. To clarify the precise role of ET-1 in the development of EBI
after SAH, more research is needed.